tbuckley/cabot-search huggingface dataset:
Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients
Authors: Steven E. Nissen, Venu Menon, Stephen J. Nicholls, Danielle Brennan, Luke Laffin, Paul Ridker, Kausik K. Ray, Denise Mason, John J. P. Kastelein, Leslie Cho, Peter Libby, Na Li, JoAnne Foody, Michael J. Louie, A. Michael Lincoff
Journal: JAMA (2023)

The effects of bempedoic acid on cardiovascular outcomes in statin-intolerant patients without a prior cardiovascular event (primary prevention) have not been fully described.To determine the effects of bempedoic acid on cardiovascular outcomes in primary prevention patients.This masked, randomized clinical trial enrolled 13 970 statin-intolerant patients (enrollment December 2016 to August 2019 at 1250 centers in 32 countries), including 4206 primary prevention patients.Participants were randomized to oral bempedoic acid, 180 mg daily (n = 2100), or matching placebo (n = 2106).The primary efficacy measure was the time from randomization to the first occurrence of any component of a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization.Mean participant age was 68 years, 59% were female, and 66% had diabetes. From a mean baseline of 142.2 mg/dL, compared with placebo, bempedoic acid reduced low-density lipoprotein cholesterol levels by 30.2 mg/dL (21.3%) and high-sensitivity C-reactive protein levels by 0.56 mg/L (21.5%), from a median baseline of 2.4 mg/L. Follow-up for a median of 39.9 months was associated with a significant risk reduction for the primary end point (111 events [5.3%] vs 161 events [7.6%]; adjusted hazard ratio [HR], 0.70 [95% CI, 0.55-0.89]; P = .002) and key secondary end points, including the composite of cardiovascular death, MI, or stroke (83 events [4.0%] vs 134 events [6.4%]; HR, 0.64 [95% CI, 0.48-0.84]; P < .001); MI (29 events [1.4%] vs 47 events [2.2%]; HR, 0.61 [95% CI, 0.39-0.98]); cardiovascular death (37 events [1.8%] vs 65 events [3.1%]; HR, 0.61 [95% CI, 0.41-0.92]); and all-cause mortality (75 events [3.6%] vs 109 events [5.2%]; HR, 0.73 [95% CI, 0.54-0.98]). There was no significant effect on stroke or coronary revascularization. Adverse effects with bempedoic acid included a higher incidence of gout (2.6% vs 2.0%), cholelithiasis (2.5% vs 1.1%), and increases in serum creatinine, uric acid, and hepatic enzyme levels.In a subgroup of high-risk primary prevention patients, bempedoic acid treatment was associated with reduced major cardiovascular events.ClinicalTrials.gov Identifier: NCT02993406.
Global treatment outcomes of extensively drug-resistant tuberculosis in adults: A systematic review and meta-analysis
Authors: Ole Skouvig Pedersen, Freja Breth Holmgaard, Mads Kristian Duborg Mikkelsen, Christoph Lange, Giovanni Sotgiu, Troels Lillebaek, Aase Bengaard Andersen, Christian Morberg Wejse, Victor Naestholt Dahl
Journal: Journal of Infection (2023)

Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the 2006 extensively drug-resistant tuberculosis definitions and old treatment regimens are being replaced, we aimed to estimate the proportion of extensively drug-resistant tuberculosis patients globally who achieved successful treatment outcomes.
Food Insecurity and Diabetes: Overview of Intersections and Potential Dual Solutions
Authors: Ronli Levi, Sara N. Bleich, Hilary K. Seligman
Journal: Diabetes Care (2023)

Food insecurity increases the risk of developing diabetes and its complications. In this article, we describe the complex relationship that exists between food insecurity and diabetes and describe potential mechanisms that may underlie this association. We then describe how two different types of interventions, food-is-medicine and federal nutrition assistance programs, may help address both food insecurity and health. Finally, we outline the research, policy, and practice opportunities that exist to address food insecurity and reduce diabetes-related health disparities.
Overview of Social Determinants of Health in the Development of Diabetes
Authors: Felicia Hill-Briggs, Stephanie L. Fitzpatrick
Journal: Diabetes Care (2023)

To guide effective planning and decision-making regarding strategies to address adverse social determinants of health (SDOH) in diabetes, an understanding of upstream drivers and root causes is imperative. The World Health Organization SDOH framework includes socioeconomic and political systems and racism as upstream drivers of SDOH. These factors are not currently included in the Healthy People 2030 framework or other commonly used U.S. SDOH frameworks. This review gives an overview of the socioeconomic status SDOH and race and ethnicity in diabetes prevalence and incidence, discusses socioeconomic and political contexts and racism as upstream drivers and root causes of SDOH that necessitate attention in the U.S., illustrates the role of these drivers in the entrenched nature of SDOH within racial and ethnic minoritized and marginalized populations, and examines current and emerging actions within and beyond the health care sector to mitigate adverse SDOH. The incorporation of socioeconomic and political systems and racism as root causes and current drivers of adverse SDOH into U.S. SDOH frameworks enables an emphasis shift from primary individual- and neighborhood-level time-limited solutions to multisector and all-of-government initiatives that bring requisite policy change and permanent structural change.
The Impact of Neighborhoods on Diabetes Risk and Outcomes: Centering Health Equity
Authors: Mahasin S. Mujahid, Sai Ramya Maddali, Xing Gao, Khin H. Oo, Larissa A. Benjamin, Tené T. Lewis
Journal: Diabetes Care (2023)

Neighborhood environments significantly influence the development of diabetes risk factors, morbidity, and mortality throughout an individual's life. The social, economic, and physical environments of a neighborhood all affect the health risks of individuals and communities and also affect population health inequities. Factors such as access to healthy food, green spaces, safe housing, and transportation options can impact the health outcomes of residents. Social factors, including social cohesion and neighborhood safety, also play an important role in shaping neighborhood environments and can influence the development of diabetes. Therefore, understanding the complex relationships between neighborhood environments and diabetes is crucial for developing effective strategies to address health disparities and promote health equity. This review presents landmark findings from studies that examined associations between neighborhood socioeconomic, built and physical, and social environmental factors and diabetes-related risk and outcomes. Our framework emphasizes the historical context and structural and institutional racism as the key drivers of neighborhood environments that ultimately shape diabetes risk and outcomes. To address health inequities in diabetes, we propose future research areas that incorporate health equity principles and place-based interventions.
Giving a voice to patients at high risk of dying in the intensive care unit: a multiple source approach
Authors: Nancy Kentish-Barnes, Anne-Laure Poujol, Emilie Banse, Victoire Deltour, Cyril Goulenok, Charlotte Garret, Anne Renault, Virginie Souppart, Anne Renet, Alain Cariou, Diane Friedman, Ludivine Chalumeau-Lemoine, Olivier Guisset, Sybille Merceron, Antoine Monsel, Olivier Lesieur, Frédéric Pochard, Elie Azoulay
Journal: Intensive Care Medicine (2023)
Asymptomatic Plasmodium falciparum infection evades triggering a host transcriptomic response
Authors: Diana Ahu Prah, Claire Dunican, Linda Eva Amoah, Mahdi Moradi Marjaneh, Myrsini Kaforou, Asa Nordgren, William Jones-Warner, Yaw Aniweh, Gordon A Awandare, Aubrey J Cunnington, Julius Clemence Hafalla
Journal: Journal of Infection (2023)
EASL Clinical Practice Guidelines on hepatitis delta virus
Authors: Maurizia Rossana Brunetto, Gabriele Ricco, Francesco Negro, Heiner Wedemeyer, Cihan Yurdaydin, Tarik Asselah, George Papatheodoridis, Liana Gheorghe, Kosh Agarwal, Patrizia Farci, Maria Buti
Journal: Journal of Hepatology (2023)
A multisociety Delphi consensus statement on new fatty liver disease nomenclature
Authors: Mary E. Rinella, Jeffrey V. Lazarus, Vlad Ratziu, Sven M. Francque, Arun J. Sanyal, Fasiha Kanwal, Diana Romero, Manal F. Abdelmalek, Quentin M. Anstee, Juan Pablo Arab, Marco Arrese, Ramon Bataller, Ulrich Beuers, Jerome Boursier, Elisabetta Bugianesi, Christopher D. Byrne, Graciela E. Castro Narro, Abhijit Chowdhury, Helena Cortez-Pinto, Donna R. Cryer, Kenneth Cusi, Mohamed El-Kassas, Samuel Klein, Wayne Eskridge, Jiangao Fan, Samer Gawrieh, Cynthia D. Guy, Stephen A. Harrison, Seung Up Kim, Bart G. Koot, Marko Korenjak, Kris V. Kowdley, Florence Lacaille, Rohit Loomba, Robert Mitchell-Thain, Timothy R. Morgan, Elisabeth E. Powell, Michael Roden, Manuel Romero-Gómez, Marcelo Silva, Shivaram Prasad Singh, Silvia C. Sookoian, C. Wendy Spearman, Dina Tiniakos, Luca Valenti, Miriam B. Vos, Vincent Wai-Sun Wong, Stavra Xanthakos, Yusuf Yilmaz, Zobair Younossi, Ansley Hobbs, Marcela Villota-Rivas, Philip N. Newsome
Journal: Journal of Hepatology (2023)

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmatising, and can improve awareness and patient identification.
Anabolic Steroid Use and Perceived Effects in Ten Weight-Trained Women Athletes
Authors: Richard H. Strauss
Journal: JAMA (1985)

Ten women athletes who consistently used anabolic steroids were interviewed about their patterns of drug use and the perceived effects. Anabolic steroids were used in a cyclical manner, often with several drugs taken simultaneously. All participants believed that muscle size and strength were increased in association with anabolic steroid use. Most also noted a deepening of the voice, increased facial hair, increased aggressiveness, clitoral enlargement, and menstrual irregularities. The participants were willing to tolerate these side effects but thought that such changes might be unacceptable to many women. (<i>JAMA</i>1985;253:2871-2873)
Focus on Metformin: Its Role and Safety in Pregnancy and Beyond
Authors: Christine Newman, Louise Rabbitt, Adesuwa Ero, Fidelma P Dunne
Journal: Drugs (2023)

Metformin is used worldwide in the treatment of type 2 diabetes and has been used in the treatment of diabetes in pregnancy since the 1970s. It is highly acceptable to patients due to its ease of administration, cost and adverse effect profile. It is effective in reducing macrosomia, large-for-gestational-age infants and reduces maternal weight gain. Despite its many advantages, metformin has been associated with reductions in foetal size and has been associated with an increase in infants born small-for-gestational-age in certain cohorts. In this article, we review its efficacy, adverse effects and long-term follow-up before, during and after pregnancy for both mother and infant. We also evaluate the other forms of treatment for gestational diabetes, including oral therapies, insulin therapy and emerging treatments.
Continuous glucose monitoring in a healthy population: understanding the post-prandial glycemic response in individuals without diabetes mellitus
Authors: Paul R.E. Jarvis, Jessica L. Cardin, Pamela M. Nisevich-Bede, James P. McCarter
Journal: Metabolism (2023)

Continuous glucose monitoring has become a common adjunct in the management of Diabetes Mellitus. However, there has been a recent trend among individuals without diabetes using these devices as a means of monitoring their health. The increased visibility of glucose data has allowed users to study the effect lifestyle has upon post-prandial glucose levels. Although post-prandial hyperglycemia is well understood in the setting of diabetes, its impact in individuals without diabetes is less well defined. This article reviews the factors which contribute to post-prandial hyperglycemia in individuals without diabetes and how the data obtained from continuous glucose monitoring can be used to improve an individual's metabolic health.
Vitamin D3 attenuates SARS‐CoV‐2 nucleocapsid protein‐caused hyperinflammation by inactivating the NLRP3 inflammasome through the VDR‐BRCC3 signaling pathway in vitro and in vivo
Authors: Mingliang Chen, Ying He, Xiaofeng Hu, Xunhu Dong, Zexuan Yan, Qingning Zhao, Jingyuan Li, Dongfang Xiang, Yong Lin, Hongbin Song, Xiuwu Bian
Journal: MedComm (2023)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-caused coronavirus disease 2019 (COVID-19) is a global crisis with no satisfactory therapies. Vitamin D3 (VD3) is considered a potential candidate for COVID-19 treatment; however, little information is available regarding the exact effects of VD3 on SARS-CoV-2 infection and the underlying mechanism. Herein, we confirmed that VD3 reduced SARS-CoV-2 nucleocapsid (N) protein-caused hyperinflammation in human bronchial epithelial (HBE) cells. Meanwhile, VD3 inhibited the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation in N protein-overexpressed HBE (HBE-N) cells. Notably, the inhibitors of caspase-1, NLRP3, and
Microneedle/CD-MOF-mediated transdural controlled release of methylprednisolone sodium succinate after spinal cord injury
Authors: Xiao Zhai, Kai Chen, Xianzhao Wei, Hailing Zhang, Huan Yang, Kun Jiao, Chen Liu, Zhiguo Fan, Ji Wu, Tianjunke Zhou, Haojue Wang, Jingfeng Li, Ming Li, Yushu Bai, Bo Li
Journal: Journal of Controlled Release (2023)
Characterization of stability, safety and immunogenicity of the mRNA lipid nanoparticle vaccine Iribovax® against COVID-19 in nonhuman primates
Authors: Parvin Zamani, Mohammad Mashreghi, Mahere Rezazade Bazaz, Selma Zargari, Farzaneh Alizadeh, Mahyar Dorrigiv, Asghar Abdoli, Hossein Aminianfar, Mahdi Hatamipour, Javad Zarqi, Saeed Behboodifar, Yalda Samsami, Saeideh Khorshid Sokhangouy, Yahya Sefidbakht, Vuk Uskoković, Seyed Mahdi Rezayat, Mahmoud Reza Jaafari, Sina Mozaffari-Jovin
Journal: Journal of Controlled Release (2023)
Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer
Authors: Charles M. Rudin, Martin Reck, Melissa L. Johnson, Fiona Blackhall, Christine L. Hann, James Chih-Hsin Yang, Julie M. Bailis, Gwyn Bebb, Amanda Goldrick, John Umejiego, Luis Paz-Ares
Journal: Journal of Hematology & Oncology (2023)

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a poor prognosis. Initial responses to standard-of-care chemo-immunotherapy are, unfortunately, followed by rapid disease recurrence in most patients. Current treatment options are limited, with no therapies specifically approved as third-line or beyond. Delta-like ligand 3 (DLL3), a Notch inhibitory ligand, is an attractive therapeutic target because it is overexpressed on the surface of SCLC cells with minimal to no expression on normal cells. Several DLL3-targeted therapies are being developed for the treatment of SCLC and other neuroendocrine carcinomas, including antibody-drug conjugates (ADCs), T-cell engager (TCE) molecules, and chimeric antigen receptor (CAR) therapies. First, we discuss the clinical experience with rovalpituzumab tesirine (Rova-T), a DLL3-targeting ADC, the development of which was halted due to a lack of efficacy in phase 3 studies, with a view to understanding the lessons that can be garnered for the rapidly evolving therapeutic landscape in SCLC. We then review preclinical and clinical data for several DLL3-targeting agents that are currently in development, including the TCE molecules-tarlatamab (formerly known as AMG 757), BI 764532, and HPN328-and the CAR T-cell therapy AMG 119. We conclude with a discussion of the future challenges and opportunities for DLL3-targeting therapies, including the utility of DLL3 as a biomarker for patient selection and disease progression, and the potential of rational combinatorial approaches that can enhance efficacy.
The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial
Authors: Deepak L. Bhatt, Harold E. Bays, Michael Miller, James E. Cain, Katarzyna Wasilewska, Nabil S. Andrawis, Teresa Parli, Shibao Feng, Lulu Sterling, Leo Tseng, Cynthia L. Hartsfield, Germaine D. Agollah, Hank Mansbach, John J. P. Kastelein
Journal: Nature Medicine (2023)

Abstract Pegozafermin, a long-acting glycopegylated analog of human fibroblast growth factor 21, is in development for the treatment of severe hypertriglyceridemia (SHTG) and nonalcoholic steatohepatitis. Here we report the results of a phase 2, double-blind, randomized, five-arm trial testing pegozafermin at four different doses ( n = 67; 52 male) versus placebo ( n = 18; 12 male) for 8 weeks in patients with SHTG (triglycerides (TGs), ≥500 mg dl −1 and ≤2,000 mg dl −1 ). Treated patients showed a significant reduction in median TGs for the pooled pegozafermin group versus placebo (57.3% versus 11.9%, difference versus placebo −43.7%, 95% confidence interval (CI): −57.1%, −30.3%; P &lt; 0.001), meeting the primary endpoint of the trial. Reductions in median TGs ranged from 36.4% to 63.4% across all treatment arms and were consistent regardless of background lipid-lowering therapy. Results for secondary endpoints included significant decreases in mean apolipoprotein B and non-high-density lipoprotein cholesterol concentrations (−10.5% and −18.3% for pooled doses compared to 1.1% and −0.6% for placebo (95% CI: −21.5%, −2.0%; P = 0.019 and 95% CI: −30.7%, −5.1%; P = 0.007, respectively), as well as a significant decrease in liver fat fraction for pooled treatment ( n = 17) versus placebo ( n = 6; −42.2% pooled pegozafermin, −8.3% placebo; 95% CI: −60.9%, −8.7%; P = 0.012), as assessed in a magnetic resonance imaging sub-study. No serious adverse events were observed to be related to the study drug. If these results are confirmed in a phase 3 trial, pegozafermin could be a promising treatment for SHTG (ClinicalTrials.gov registration: NCT0441186).
CSF1R inhibition for histiocytic neoplasm with CBL mutations refractory to MEK1/2 inhibition
Authors: Eli L. Diamond, Jasmine H. Francis, Mario E. Lacouture, Veronica Rotemberg, Mariko Yabe, Kseniya Petrova-Drus, Gary A. Ulaner, Ryan Reddy, Omar Abdel-Wahab, Benjamin H. Durham
Journal: Leukemia (2023)

Histiocytic neoplasms are rare clonal hematopoietic disorders occupying a wide clinical spectrum amongst adults and children.Identification of recurrent somatic mutations in the mitogen activated protein kinase (MAPK) pathway has reframed our understanding of these diseases from autoimmune conditions to clonal myeloid neoplasms.Equally important knowledge of mutational drivers of histiocytoses has overhauled the clinical management of these disorders.Erdheim-Chester disease (ECD) is a multisystem histiocytic neoplasm affecting adults characterized by osseous infiltration in the distal legs and variable involvement of retroperitoneal, cardiovascular, cutaneous, neurological, and other structures [1].More than 50% of ECD lesions harbor BRAF V600E mutations, and in 2018 vemurafenib was approved by the U.S. Food and Drug Administration (FDA) for BRAF V600E -mutated ECD [2].The MEK1/2 inhibitor, cobimetinib, was recently broadly approved for the treatment of histiocytic neoplasms based on a phase 2 trial in which 20/24 patients with diverse histiocytic neoplasms including mutations in BRAF, N/KRAS, and MEK1/2 demonstrated a complete or partial response by [ 18 F]-Fluorodeoxyglucose positron-emission tomography (FDG-PET).Recent studies have identified a subset of histiocytic neoplasm patients with activating mutations upstream of RAS-RAF-MEK1/2 including in the receptor tyrosine kinase CSF1R [3].Importantly, one patient with an activating CSF1R mutation has been treated successfully with the CSF1R inhibitor, pexidartinib [4].Given the requirement of CSF1R signaling for development and maintenance of the monocyte/macrophage lineage and the observation that CSF1R is required for differentiation of lesional cells within LCH [5], it has been hypothesized that CSF1R inhibition may be efficacious in broader genetic subtypes of histiocytosis patients.To date, however, evaluation of CSF1R inhibition in histiocytic neoplasms outside of one patient with CSF1R-mutated disease has not been explored.We present here a case of ECD with
Anti-PEG IgM production induced by PEGylated liposomes as a function of administration route
Authors: Haruka Takata, Taro Shimizu, Rina Yamade, Nehal E. Elsadek, Sherif E. Emam, Hidenori Ando, Yu Ishima, Tatsuhiro Ishida
Journal: Journal of Controlled Release (2023)
Addendum. 2. Classification and Diagnosis of Diabetes: <i>Standards of Care in Diabetes—2023</i>. Diabetes Care 2023;46(Suppl. 1):S19–S40
Authors: Nuha A. ElSayed, Grazia Aleppo, Vanita R. Aroda, Raveendhara R. Bannuru, Florence M. Brown, Dennis Bruemmer, Billy S. Collins, Marisa E. Hilliard, Diana Isaacs, Eric L. Johnson, Scott Kahan, Kamlesh Khunti, Jose Leon, Sarah K. Lyons, Mary Lou Perry, Priya Prahalad, Richard E. Pratley, Jane Jeffrie Seley, Robert C. Stanton, Robert A. Gabbay
Journal: Diabetes Care (2023)

Section 2, “Classification and Diagnosis of Diabetes,” of the Standards of Care in Diabetes—2023 has been updated to refine the diagnostic criteria for type 1 diabetes based on recent U.S. Food and Drug Administration approval of a new drug to delay the incidence of type 1 diabetes.
Addendum. 3. Prevention or Delay of Type 2 Diabetes and Associated Comorbidities: <i>Standards of Care in Diabetes—2023</i>. Diabetes Care 2023;46(Suppl. 1):S41–S48
Authors: Nuha A. ElSayed, Grazia Aleppo, Vanita R. Aroda, Raveendhara R. Bannuru, Florence M. Brown, Dennis Bruemmer, Billy S. Collins, Marisa E. Hilliard, Diana Isaacs, Eric L. Johnson, Scott Kahan, Kamlesh Khunti, Jose Leon, Sarah K. Lyons, Mary Lou Perry, Priya Prahalad, Richard E. Pratley, Jane Jeffrie Seley, Robert C. Stanton, Robert A. Gabbay
Journal: Diabetes Care (2023)

Section 3, "Prevention or Delay of Type 2 Diabetes and Associated Comorbidities," of the Standards of Care in Diabetes—2023 has been updated based on recent U.S. Food and Drug Administration approval of a new drug to delay the incidence of type 1 diabetes.